Data to suggest that the phosphorylation of nuclear proteins plays a role in the regulation of gene expression, probably at the level of transcription, are numerous but remain of a correlative, and therefore of circumstantial, nature. If it were possible to specifically inhibit nuclear protein phosphorylation one could assess the effect of that inhibition initially on RNA synthesis rates and, perhaps, subsequently on gene expression. Two oligoribonucleotides that specifically inhibit the nuclear protein kinases have been identified in this laboratory; virtually no inhibition is obtaied with a 100-fold excess in terms of A260 of random RNA digests. These oligonucleotides will be isolated in pure form, their structure will be determined by sequence analysis and their interaction with the nuclear protein kinases will be studied by kinetic analyses. We shall attempt to ascertain the extent to which the oligonucleotides - compared to other factors - regulate the phosphorylation of nuclear proteins. An attempt will be made to use these inhibitors to determine whether or not a causal connection exists between nuclear protein phosphorylation and rates of RNA synthesis. The hyperosmolar shock method of Pardee will be used to introduce the inhibitors into cells growing in tissue culture.